N-terminal-acetylases (NATs) catalyse the covalent attachment of an acetyl moiety from acetyl-CoA to the free α-amino group at the N-terminus of a protein. This irreversible modification neutralizes the positive charge at the N-terminus, makes the N-terminal residue larger and more hydrophobic, and prevents its removal by hydrolysis. It may also play a role in membrane targeting and gene silencing. NatE is found in all eukaryotic organisms and plays an important role in chromosome resolution and segregation. It specifically targets N-terminal L-methionine residues attached to Lys, Val, Ala, Tyr, Phe, Leu, Ser, and Thr. There is some substrate overlap with EC 2.3.1.256, N-terminal methionine Nα-acetyltransferase NatC. In addition, the acetylation of Met followed by small residues such as Ser, Thr, Ala, or Val suggests a kinetic competition between NatE and EC 3.4.11.18, methionyl aminopeptidase. The enzyme also has the activity of EC 2.3.1.48, histone acetyltransferase, and autoacetylates several of its own lysine residues.